The long-term objective of this project is to characterize neural correlates of perceptual learning in the human visual system. Perceptual learning can be defined as a specific improvement in the performance of a perceptual discrimination through training. Humans are capable of learning new and intricate skills throughout the lifespan, and perceptual learning experimental paradigms provide model systems for studying these processes. In addition, training procedures involving perceptual learning have been used to treat learning disorders like dyslexia and developmental disorders such as amblyopia. Therefore, understanding the neural mechanisms underlying perceptual learning has consequences for basic science as well as public health implications. Two perceptual learning tasks will be employed in these studies: a motion direction discrimination task and a texture orientation discrimination task. These tasks differentially involve two different visual processing streams in the human brain. One of these specialized for perception of motion and spatial location, and the other is specialized for perception of visual form. Human subjects will be trained on these tasks, and the improvements in behavioral performance resulting from this training will be measured. To study neural correlates of this enhancement in behavioral performance, functional magnetic resonance imaging (fMRI) will be used to measure the activity in defined brain areas before and after perceptual learning occurs. The fMRI experiments will include measurements of the amplitude of responses evoked by visual stimuli and estimates of selectivity of populations of neurons in a number of cortical areas. [Changes in functional connectivity among these areas following perceptual learning will also be measured.] Selectivity will be defined in the spatial domain and in the featural domain (selectivity for stimulus orientation or direction of motion). Acetylcholine is a neurotransmitter that plays an important role in attention networks in the brain. Drugs that prolong the synaptic actions of endogenous acetylcholine (cholinesterase inhibitors) are the most common treatment of Alzheimer's disease. Although the actions of these drugs at the biochemical level are well characterized, their cognitive effects and neural correlates of these effects are poorly understood. The cholinesterase inhibitor donepezil (trade name: Aricept) will be administered during the perceptual learning training procedures to shed light on the role of acetylcholine on learning neural plasticity and to better understand the mechanisms by which these drugs improve cognitive function in patients with Alzheimer's disease. PUBLIC HEALTH RELEVANCE: We will use magnetic resonance imaging (MRI) to measure brain activity in healthy human subjects before and after they undergo a training procedure that improves their ability to make visual discriminations. A variety of MRI measurements will be made to characterize the changes that take place in the brains of subjects as a result of this learning. In addition, the subjects will be administered donepezil, an Alzheimer's medication known to enhance cognition, and the effects of this drug on the perceptual and brain correlates of learning will be determined.